Nosocomial pneumonia is the second most common hospital-acquired infection and most common intensive care unit infection. It is associated with significant morbidity and mortality. Aspiration of oropharyngeal contents is considered a major risk factor for pneumonia, especially in mechanically ventilated patients. Whether application of oral antimicrobial agents such as chlorhexidine reduces the risk of pneumonia in the general intensive care unit patient population remains controversial. The proposed Phase III clinical trial will be a five-year, four-center placebo-controlled randomized clinical trial with a chlorhexidine oral application as the intervention. The research will extend previous findings in a general ICU population study sample by using well-validated clinical and scoring criteria for major outcomes. The proposed trial will be powered to evaluate a composite primary outcome of ventilator-associated pneumonia (VAP) and/or mortality with 535 patients in the control group and 535 patients in the intervention group. A 2 year planning grant is requested to refine the study design and methodology, develop a Manual of Operating Procedures, refine patient recruitment approaches, organize potential study centers for standardization of approach and diagnostic criteria, and establish administrative and monitoring committees. Personnel from the four clinical sites and the data coordinating center will participate in these activities as part of the Clinical Trial Planning Committee. The Phase III clinical trial would be the first outcome study properly powered to evaluate the effect of chlorhexidine oral application on pneumonia and/or mortality, and associated morbidity outcomes in mechanically ventilated patients with various indications for ICU admission (including surgical, medical, and neurological). It may provide evidence for changing health care policy by showing that a simple, inexpensive oral care preventive intervention reduces the morbidity, mortality, and costs associated with nosocomial pneumonia. [unreadable] [unreadable] [unreadable]